The overall scientific goal of this ambitious program project is to develop highly innovative methods for cancer clinical trials that can hasten successful introduction of effective new therapies into practice. The method of approach is to leverage recent advances in statistical and computational science to create new clinical trial designs and data analysis tools that resolve many of the key scientific limitations of current clinical trial methodology. The projects focus on practical design and analysis problems in Phase II and Phase 111 clinical trials, the problem of missing data and efficient use of prognostic information, postmarketing surveillance and comparative effectiveness research using clinical trial data, pharmacogenetics and individualized therapies, and the potential of dynamic treatment regimens to improve cancer treatment. The proposed clinical trial design and analysis innovations have the potential to change the prevailing clinical trial paradigm and greatly increase the rate of discovery and translation of new treatments into clinical practice. Our multi-institutional approach includes an effective and energetic process for intense, coordinated implementation, communication and dissemination of results, including developing new software for practical implementation of the newly developed methods. Our comprehensive and novel approach will lead to significant improvements in cancer clinical trial practice that will result in improved health of cancer patients.